title: FAT10 modifies p53 and upregulates its transcriptional activity.
abstract: FAT10, also known as diubiquitin, has been implicated in the regulation of diverse cellular processes, including mitosis, immune response, and apoptosis. We seek to identify FAT10-targeted proteins, an essential step in elucidating the physiological function of FAT10. To this end, human FAT10 or its non-conjugatable derivative, FAT10ΔGG, was overexpressed in HEK293 cells. We observed a number of high molecular weight FAT10 conjugates in cells expressing wild-type FAT10, but not in FAT10ΔGG. The FAT10 conjugates are inducible by TNF-α and accumulated significantly when cells were treated with proteasome inhibitor, MG132. Among them, tumor suppressor p53 was found to be FATylated. The p53 transcriptional activity was found to be substantially enhanced in FAT10-overexpressing cells. In addition, overexpressing FAT10 in HEK293 cells also reduced the population of p53 which cross reacted with monoclonal anti-p53 antibody, PAB240, known to recognize only the transcriptionally inactive p53. FAT10 in the nucleus was found co-localized with p53 and altered its subcellular compartmentalization. Furthermore, overexpressing FAT10 led to a reduction in the size of promyelocytic leukemia nuclear bodies (PML-NBs) and altered their distribution in the nucleus. Based on these observations, a potential mechanism which correlates FATylation of p53 to its translocation and transcriptional activation is discussed.
authors.affiliation: Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Li
authors.forename: Rasa
authors.initials: R
authors.lastname: Santockyte
authors.forename: Shiqin
authors.initials: S
authors.lastname: Yu
authors.forename: Rong-Fong
authors.initials: RF
authors.lastname: Shen
authors.forename: Ephrem
authors.initials: E
authors.lastname: Tekle
authors.forename: Caroline G L
authors.initials: CG
authors.lastname: Lee
authors.forename: David C H
authors.initials: DC
authors.lastname: Yang
authors.forename: P Boon
authors.initials: PB
authors.lastname: Chock
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014452:Ubiquitins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016159:Tumor Suppressor Protein p53; C109184:UBD protein, human; D014452:Ubiquitins